Bridging Metabolic-Associated Steatotic Liver Disease and Cardiovascular Risk: A Potential Role for Ketogenesis.

The prevalence of cardiovascular diseases (CVDs) is a growing global health concern. Recent advances have demonstrated significant reductions in acute cardiovascular events through the management of modifiable cardiovascular risk factors. However, these factors are responsible for about 50% of the global cardiovascular disease burden. Considering that CVDs are one of the top mortality causes worldwide, the concept of residual cardiovascular risk is an important emerging area of study. Different factors have been proposed as sources of residual risk markers, including non-HDL particles characterization, as well as inflammation measured by serum and imaging technics. Among these, metabolic-associated steatotic liver disease (MASLD) remains controversial. Two opposing viewpoints contend: one positing that fatty liver disease merely reflects classical risk factors and thus adds no additional risk and another asserting that fatty liver disease independently impacts cardiovascular disease incidence. To address this dilemma, one hypothetical approach is to identify specific hepatic energy-yielding mechanisms and assess their impact on the cardiovascular system. Ketogenesis, a metabolic intermediate process particularly linked to energy homeostasis during fasting, might help to link these concepts. Ketogenic metabolism has been shown to vary through MASLD progression. Additionally, newer evidence supports the significance of circulating ketone bodies in cardiovascular risk prediction. Furthermore, ketogenic metabolism modification seems to have a therapeutic impact on cardiovascular and endothelial damage. Describing the relationship, if any, between steatotic liver disease and cardiovascular disease development through ketogenesis impairment might help to clarify MASLD's role in cardiovascular risk. Furthermore, this evidence might help to solve the controversy surrounding liver steatosis impact in CVD and might lead to a more accurate risk assessment and therapeutic targets in the pursuit of precision medicine.

Interactions of Comorbidity and Five Simple Environmental Unhealthy Habits Concerning Physical and Mental Quality of Life in the Clinical Setting.

The objective of this study was to examine the interactions between comorbidity and five lifestyle single habits concerning different subscales of quality of life (QoL). For the study, 302 patients were consecutively recruited at the internal medicine department of a tertiary teaching hospital. Lifestyle habits, comorbidities and QoL were recorded according to validated questionnaires. Five single unhealthy habits, such as tobacco consumption, dietary intake of ultra-processed pastries, raw nuts or carbonated drinks, sleep time and physical activity patterns were selected according to previously published data. The main outcomes of the study were the scores of the eight subscales of the SF-36 QoL survey. The aggregate of unhealthy habits showed statistically significant association to every category in the SF-36 questionnaire, both in the univariate and the multivariate analysis when adjusting by age, sex and comorbidity. An interaction was found between comorbidity and unhealthy habits in both physical and mental summaries of SF-36. In conclusion, the lifestyle assessment according to five unhealthy habits is associated with a worse QoL. The interaction between comorbidity and unhealthy habits is especially clear in diseased patients due to the interplay between illness and lifestyle in the prediction of QoL.

A 42-Year-Old Woman with Untreated Growth Hormone Insensitivity, Diabetic Retinopathy, and Gene Sequencing Identifies a Variant of Laron Syndrome.

BACKGROUND Growth hormone insensitivity and reduced levels of insulin-like growth factor-1 (IGF-1) are associated with metabolic syndrome that includes obesity, hyperglycemia, type 2 diabetes mellitus, and dyslipidemia. Laron syndrome is a rare autosomal recessive condition associated with insensitivity to growth hormone that results in short stature and metabolic syndrome and is usually diagnosed in childhood. This report is of a 42-year-old Mexican woman with untreated growth hormone insensitivity and diabetic retinopathy, in whom gene sequencing supported the identification of a variant of Laron syndrome. CASE REPORT A 42-year-old Mexican woman with untreated growth hormone insensitivity, metabolic syndrome, and type 2 diabetes mellitus was diagnosed with cataracts, severe retinopathy and hearing loss. She was investigated for genetic causes of reduction in IGF-1. Next-generation sequencing (NGS) showed genetic changes in the growth hormone and IGF-1 axis. The patient's phenotype and genetic changes were consistent with Laron syndrome. CONCLUSIONS The early detection of reduced IGF-1 and identification of the cause of growth hormone insensitivity require international consensus on the approach to diagnosis and treatment methods, including effective IGF-1 replacement therapy. Early diagnosis may reduce the clinical consequences of complications that include short stature the development of metabolic syndrome, type 2 diabetes mellitus, and retinopathy.

Fanconi Anemia and Laron Syndrome.

BACKGROUND: Fanconi anemia (FA) is a condition characterized by genetic instability and short stature, which is due to growth hormone (GH) deficiency in most cases. However, no apparent relationships have been identified between FA complementation group genes and GH. In this study, we thereby considered an association between FA and Laron syndrome (LS) (insulin-like growth factor 1 [IGF-1] deficiency). METHODS: A 21-year-old female Mexican patient with a genetic diagnosis of FA was referred to our research department for an evaluation of her short stature. Upon admission to our facility, her phenotype led to a suspicion of LS; accordingly, serum levels of IGF-1 and IGF binding protein 3 were analyzed and a GH stimulation test was performed. In addition, we used a next-generation sequencing approach for a molecular evaluation of FA disease-causing mutations and genes involved in the GH-IGF signaling pathway. RESULTS: Tests revealed low levels of IGF-1 and IGF binding protein 3 that remained within normal ranges, as well as a lack of response to GH stimulation. Sequencing confirmed a defect in the GH receptor signaling pathway. CONCLUSIONS: To the best of our knowledge, this study is the first to suggest an association between FA and LS. We propose that IGF-1 administration might improve some FA complications and functions based upon IGF-1 beneficial actions observed in animal, cell and indirect clinical models: erythropoiesis modulation, immune function improvement and metabolic regulation.

Trial of complete weaning from immunosuppression for liver transplant recipients: factors predictive of tolerance.

Recipients of liver transplantation (LT) may develop immunological tolerance. Factors predictive of tolerance are not clearly understood. Transplant recipients with normal liver function tests and without active viral hepatitis or autoimmune disease who presented with side effects of immunosuppression or a high risk of de novo malignancies were selected to participate in this prospective study. Twenty-four patients fulfilled the inclusion criteria and, therefore, underwent a gradual reduction of immunosuppression. Tolerance was defined as normal liver function tests after immunosuppression withdrawal. Basal clinical and immunological characteristics, including lymphocyte counts and subpopulations (T, B, natural killer, CD4(+) , CD8(+) , and regulatory T cells) and the phytohemagglutinin stimulation index (SI), were compared for tolerant and nontolerant patients. Fifteen of the 24 patients (62.5%) were tolerant at a median of 14 months (interquartile range = 8.5-22.5 months) after complete immunosuppression withdrawal. Tolerant patients had a longer median interval between transplantation and inclusion in the study (156 for tolerant patients versus 71 months for nontolerant patients, P = 0.003) and a lower median SI (7.49 for tolerant patients versus 41.73 for nontolerant patients, P = 0.01). We identified 3 groups of patients with different probabilities of tolerance: in the first group (n = 7 for an interval > 10 years and an SI < 20), 100% reached tolerance; in the second group (n = 10 for an interval > 10 years and an SI > 20 or an interval < 10 years and an SI < 20), 60% reached tolerance; and in the third group (n = 7 for an interval < 10 years and an SI > 20), 29% reached tolerance. In conclusion, a high proportion of select LT recipients can reach tolerance over the long term. Two simple basal variables-the time from transplantation and the SI-may help to identify these patients.

Listeria monocytogenes septic arthritis in a patient treated with mycophenolate mofetil for polyarteritis nodosa: a case report and review of the literature.

Listeriosis can be a cause of arthritis. Here, we present a case of Listeria monocytogenes septic arthritis of the right hip in a 66-year-old male treated with mycophenolate mofetil for polyarteritis nodosa. So far, septic arthritis due to this microorganism has not been reported in patients treated with mycophenolate mofetil. We review the literature of L. monocytogenes septic arthritis and discuss the role of mycophenolate mofetil treatment in precipitating listeriosis.